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Nitric oxide sustains IL-1β expression in human dendritic cells enhancing their capacity to induce IL-17-producing T-cells.

Obregon C, Graf L, Chung KF, Cesson V, Nicod LP - PLoS ONE (2015)

Bottom Line: NO changed the pattern of cytokine release by LPS-matured DCs, dependent on the concentration of NO, as well as on the timing of its addition to the cells during maturation.Indeed, DCs treated with NO efficiently induced the release of IL-17 by T-cells through IL-1β.Our work highlights the important role that NO may play in sustaining inflammation during an infection through the preferential differentiation of the Th17 lineage.

View Article: PubMed Central - PubMed

Affiliation: Pneumology Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

ABSTRACT
The role played by lung dendritic cells (DCs) which are influenced by external antigens and by their redox state in controlling inflammation is unclear. We studied the role played by nitric oxide (NO) in DC maturation and function. Human DCs were stimulated with a long-acting NO donor, DPTA NONOate, prior to exposure to lipopolysaccharide (LPS). Dose-and time-dependent experiments were performed with DCs with the aim of measuring the release and gene expression of inflammatory cytokines capable of modifying T-cell differentiation, towardsTh1, Th2 and Th17 cells. NO changed the pattern of cytokine release by LPS-matured DCs, dependent on the concentration of NO, as well as on the timing of its addition to the cells during maturation. Addition of NO before LPS-induced maturation strongly inhibited the release of IL-12, while increasing the expression and release of IL-23, IL-1β and IL-6, which are all involved in Th17 polarization. Indeed, DCs treated with NO efficiently induced the release of IL-17 by T-cells through IL-1β. Our work highlights the important role that NO may play in sustaining inflammation during an infection through the preferential differentiation of the Th17 lineage.

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Related in: MedlinePlus

IL-1β is required to prime T-cells to produce IL-17 in a mixed lymphocyte reaction condition.Production of IL-17 by T-cells primed for 6 days with allogenic DCs at a DC:T-cell ratio of 1:10. As described in Materials and Methods, DCs were simulated with DPTA NONOate (0.6mM) 1h before LPS (100ng/ml) stimulation. During the MLR, cells were cultured in the presence of neutralizing antibodies to IL-23, IL-1β and IL-6R. Data are expressed as mean ±SEM of 3 independent experiments. *P < 0.05.
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pone.0120134.g006: IL-1β is required to prime T-cells to produce IL-17 in a mixed lymphocyte reaction condition.Production of IL-17 by T-cells primed for 6 days with allogenic DCs at a DC:T-cell ratio of 1:10. As described in Materials and Methods, DCs were simulated with DPTA NONOate (0.6mM) 1h before LPS (100ng/ml) stimulation. During the MLR, cells were cultured in the presence of neutralizing antibodies to IL-23, IL-1β and IL-6R. Data are expressed as mean ±SEM of 3 independent experiments. *P < 0.05.

Mentions: To further document the function of NO. and hence the role of IL-23, IL-1β and IL-6 in the ability of LPS-DCs to induce Th17 responses, we evaluated the effects of anti-IL-23, anti-IL-1β and anti-IL-6 receptor (IL-6R) neutralizing antibodies. Treatment with neutralizing antibodies to IL-1β or both IL-1β and IL-6R abolished the release of IL-17 by T-cells induced by LPS-activated DCs, whereas neutralization of IL-23 did not affect the release (Fig. 6). These results indicate that the ability of NO. to induce IL-17 release is critically dependent on the production of IL-1β and on the synergistic effect of IL-6 with IL-1, but is not dependent on IL-23 or IL-6 alone.


Nitric oxide sustains IL-1β expression in human dendritic cells enhancing their capacity to induce IL-17-producing T-cells.

Obregon C, Graf L, Chung KF, Cesson V, Nicod LP - PLoS ONE (2015)

IL-1β is required to prime T-cells to produce IL-17 in a mixed lymphocyte reaction condition.Production of IL-17 by T-cells primed for 6 days with allogenic DCs at a DC:T-cell ratio of 1:10. As described in Materials and Methods, DCs were simulated with DPTA NONOate (0.6mM) 1h before LPS (100ng/ml) stimulation. During the MLR, cells were cultured in the presence of neutralizing antibodies to IL-23, IL-1β and IL-6R. Data are expressed as mean ±SEM of 3 independent experiments. *P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390375&req=5

pone.0120134.g006: IL-1β is required to prime T-cells to produce IL-17 in a mixed lymphocyte reaction condition.Production of IL-17 by T-cells primed for 6 days with allogenic DCs at a DC:T-cell ratio of 1:10. As described in Materials and Methods, DCs were simulated with DPTA NONOate (0.6mM) 1h before LPS (100ng/ml) stimulation. During the MLR, cells were cultured in the presence of neutralizing antibodies to IL-23, IL-1β and IL-6R. Data are expressed as mean ±SEM of 3 independent experiments. *P < 0.05.
Mentions: To further document the function of NO. and hence the role of IL-23, IL-1β and IL-6 in the ability of LPS-DCs to induce Th17 responses, we evaluated the effects of anti-IL-23, anti-IL-1β and anti-IL-6 receptor (IL-6R) neutralizing antibodies. Treatment with neutralizing antibodies to IL-1β or both IL-1β and IL-6R abolished the release of IL-17 by T-cells induced by LPS-activated DCs, whereas neutralization of IL-23 did not affect the release (Fig. 6). These results indicate that the ability of NO. to induce IL-17 release is critically dependent on the production of IL-1β and on the synergistic effect of IL-6 with IL-1, but is not dependent on IL-23 or IL-6 alone.

Bottom Line: NO changed the pattern of cytokine release by LPS-matured DCs, dependent on the concentration of NO, as well as on the timing of its addition to the cells during maturation.Indeed, DCs treated with NO efficiently induced the release of IL-17 by T-cells through IL-1β.Our work highlights the important role that NO may play in sustaining inflammation during an infection through the preferential differentiation of the Th17 lineage.

View Article: PubMed Central - PubMed

Affiliation: Pneumology Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

ABSTRACT
The role played by lung dendritic cells (DCs) which are influenced by external antigens and by their redox state in controlling inflammation is unclear. We studied the role played by nitric oxide (NO) in DC maturation and function. Human DCs were stimulated with a long-acting NO donor, DPTA NONOate, prior to exposure to lipopolysaccharide (LPS). Dose-and time-dependent experiments were performed with DCs with the aim of measuring the release and gene expression of inflammatory cytokines capable of modifying T-cell differentiation, towardsTh1, Th2 and Th17 cells. NO changed the pattern of cytokine release by LPS-matured DCs, dependent on the concentration of NO, as well as on the timing of its addition to the cells during maturation. Addition of NO before LPS-induced maturation strongly inhibited the release of IL-12, while increasing the expression and release of IL-23, IL-1β and IL-6, which are all involved in Th17 polarization. Indeed, DCs treated with NO efficiently induced the release of IL-17 by T-cells through IL-1β. Our work highlights the important role that NO may play in sustaining inflammation during an infection through the preferential differentiation of the Th17 lineage.

Show MeSH
Related in: MedlinePlus